Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Life Sci Space Res (Amst). 2016 Feb;8:8-13. doi: 10.1016/j.lssr.2015.12.001. Epub 2015 Dec 14.
Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a "priming" dose of protons on the cardiac cellular and molecular response to a "challenge" dose of (56)Fe in a mouse model.
Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of (56)Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of (56)Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death.
Exposure to (56)Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before (56)Fe prevented all of the responses to (56)Fe.
This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions.
最近的证据表明，心脏可能会在比以前认为的更低的辐射剂量下受到损伤。这引发了人们对太空旅行中因辐射暴露而导致心血管风险的担忧。由于太空旅行会同时接触太阳粒子事件产生的质子和银河宇宙射线产生的重离子，我们在此研究了在小鼠模型中，先接受低剂量质子照射（“激发”剂量）后，对随后的重离子（(56)Fe）照射（“挑战”剂量）的心脏细胞和分子反应的影响。
10 周龄雄性 C57BL/6 小鼠接受假照射、0.1 Gy 质子（150 MeV）、0.5 Gy (56)Fe（600 MeV/n）或在接受 0.5 Gy (56)Fe 之前 24 小时接受 0.1 Gy 质子照射。在照射后 7 天获得心脏，并使用 Western blot 检测心脏重构、炎症浸润和细胞死亡的蛋白标志物。
(56)Fe 暴露导致α-平滑肌肌动蛋白、III 型胶原、炎症细胞标志物肥大细胞胰蛋白酶、CD2 和 CD68、内皮糖蛋白血栓调节蛋白和裂解的 caspase 3 的表达增加。在所研究的所有蛋白中，只有 0.1 Gy 的质子照射剂量会小幅度增加裂解的 caspase 3 水平。另一方面，在 (56)Fe 之前 24 小时暴露于质子可阻止 (56)Fe 引起的所有反应。
本研究表明，低剂量的质子可能会使心脏对随后的重离子挑战剂量产生不同的反应。需要进一步研究以确定在其他时间点的反应、对心脏功能的影响、阈值剂量水平以及质子激发剂量可能改变重离子反应的机制。
